The cardiovascular system is under the control of both the sympathetic and the parasympathetic system. In a normal patient, these two systems are balanced, which results in particular in a heartbeat well suited to the patient's current activity (Chronotropic effect), satisfactory cardiac contractility (inotropic effect), etc. Sympathovagal balance or SVB is the balance between the sympathetic and parasympathetic branches of the autonomic nervous system. SVB may play an important role in a number of pathologies such as heart failure or myocardial infarction. The evaluation of SVB can be an important tool for the diagnosis, monitoring, and selection of a therapy for pathologies of this type.
In a patient with heart failure, or with post-myocardial infarction, sympathetic activity is excessive (hypertonic sympathetic state), compared to a depressed parasympathetic system, which leads to an abnormally faster heart rate. The sympathovagal balance is nevertheless difficult to determine, especially in acute crisis situations or in the presence of a chronic evolution of disease. The sympathovagal balance may be evaluated at regular intervals, for example daily, with an external or implantable device providing continuous monitoring of the patient.
The conventional method of assessing the situation of the autonomic nervous system of a patient, and thus its sympathovagal balance, is often based on the analysis of indicators of Heart Rate Variability (HRV) in the frequency or time domain. The evaluation of the sympathovagal balance may be based on the application of “autonomic maneuvers” which trigger a response from the patient's autonomic nervous system (“autonomic response”).
Autonomic maneuvers may implement pharmacological or mechanical manipulation (e.g., a Valsalva maneuver, a tilt test, etc.) to create a controlled modification of the cardiovascular system designed to provoke a response of the autonomic nervous system, which is collected and analyzed. A direct evaluation of the activity of the autonomic nervous system may also be made in the brain, but with highly invasive techniques. These various maneuvers cannot be applied in the context of regular monitoring of a patient with an implantable or ambulatory system, as this would involve asking the patient to repeatedly and reproducibly perform these autonomous maneuvers. Additionally, the maneuvers are often not possible because of the patient's medical condition, or even more during sleep (which is the most favorable period for assessing the sympathovagal balance given the minimum impact of external factors).
Various methods, such as the one disclosed by US2008/0281372 A1, have been proposed to analyze the HRV after spontaneous or induced disturbances of the cardiovascular system without the patient's active participation. In particular, the analysis of Heart Rate Turbulence (HRT) may be used as a disturbance to the occurrence of spontaneous ectopic beat. Although this method can be easily applied to an implantable system for regular monitoring of the sympathovagal balance, it is based on unpredictable events (e.g., ectopic beats, etc.), which may occur at random times, or not at all, causing significant bias in the estimation of sympathovagal balance. Other methods may apply a ventricular stimulation to reproduce the ectopic event used as cardiovascular disturbance for the analysis of the autonomic response. This solution, based on the production of an ectopic beat, is however deleterious especially for heart failure patients.
In any event, these techniques presuppose the existence of an implantable device in the patient (cardiac or similar pacemaker), which greatly reduces the patient population to which they may be applied. The need therefore remains to have an external, noninvasive device to assess the balance of any patient, for example using a Holter-type recorder, requiring no intervention other than the installation of electrodes, sensors, or other transducers on the body of the patient and their connection to a device ambulatory worn by the latter.
In this regard, techniques have been proposed that are not based on the patient's heart rhythm. These include analysis of the variability in blood pressure or in the cardiac contractility, when such information is available. But in these proposals, it is always necessary to cause reproducible autonomous maneuvers to obtain reliable estimates of the evolution of sympathovagal balance. The need thus remains to have a system to fully automatically and noninvasively assess the sympathovagal balance without any patient or caregiver involvement. It would be particularly advantageous for that purpose to have a device that is compatible with a long duration clinical follow-up or monitoring. For example by delivering a daily index or indicator representative of the sympathovagal balance of the patient from cardiovascular signals collected by the device in response to a controlled, reproducible, and not deleterious modification to the patient's autonomic nervous system.
US 2010/0268104 A1 discloses such a device that stimulates the auditory system of the patient through an acoustic transducer emitting in the ear of the patient more or less high and more or less strong tones. As well as simultaneously collecting an electrocardiogram which is analyzed to assess HRV variability. Instead, a device of a different type is contemplated, based on the use of a kinesthetic effector including a vibrator placed against the patient's skin. The vibrator produces a vibrating mechanical stimulation on the skin which is detected by the sensory receptors or mechanoreceptors in the body and transmitted to the autonomous central nervous system via the sensory nerves.